Challenging the 50-50 rule for the basal-bolus insulin ratio in patients with type 2 diabetes who maintain stable glycaemic control.

BACKGROUND: For patients using basal-bolus insulin therapy, it is widespread clinical practice to aim for a 50-50 ratio between basal and total daily bolus. However, this practice was based on a small study of individuals without diabetes. To assess the rule in real-world practice, we retrospectively analyzed patients on basal-bolus therapy that was adjusted at least weekly by an artificial intelligence-driven titration within the d-Nav® Insulin Management Technology. MATERIALS AND METHODS: We obtained de-identified data from the Diabetes Centre of Ulster Hospital for patients with four inclusion criteria: type 2 Diabetes (T2D), on d-Nav >6 months, on basal-bolus insulin therapy >80% of the time (based on insulin analogs), and no gap in data >3 months. RESULTS: We assembled a cohort of 306 patients, followed by the d-Nav service for 3.4 ± 1.8 years (mean ± SD), corresponding to about 180 autonomous insulin dose titrations and about 5000 autonomous individual dose recommendations per patient. After an initial run-in period, mean glycated hemoglobin (HbA1c) values in the cohort were maintained close to 7%. Surprisingly, in just over three-quarters of the cohort, the average basal insulin fraction was <50%; in half of the cohort average basal insulin fraction <41.2%; and in one-quarter the basal insulin fraction was <33.6%. Further, the basal insulin fraction did not remain static over time. In half of the patients, the basal insulin fraction varied by ≥1.9×; and, in 25% of the patients, ≥2.5×. CONCLUSION: Our data show that a 50-50 ratio of basal-to-bolus insulin does not generally apply to patients with T2D who successfully maintain stable glycemia. Therefore, the 50-50 ratio should not serve as an ongoing treatment guide. Moreover, our results emphasize the importance of at least weekly insulin titrations.

Barriers toward Physical Activity in COPD: A Quantitative Cross-Sectional, Questionnaire-Based Study.

Chronic Obstructive Pulmonary Disease (COPD) is a progressive but preventable and treatable disease and the third leading cause of death globally. Even though it is evident that physical activity (PA) relieves dyspnea, anxiety, fatigue, and increases quality of life and functional capacity, it is seldom implemented in daily life in people with COPD. The aim of this study was to identify barriers toward PA in people with COPD and to examine the role of FEV1 and smoking status in PA. The study is a quantitative cross-sectional study conducted in Denmark among people with COPD. Data was collected using questionnaires developed by the authors after pilot testing. In total, 493 people with COPD were included. The most significant barrier toward PA was low motivation (p < 0,001 and p = 0,009) and comorbidity (p = 0,035 and p = 0,016). Fear of breathlessness was significantly (p < 0,001) correlated to low motivation. FEV1, and smoking status were not associated with the level of PA. In our study, the main reason why people with COPD did not engage in PA was low motivation, where fear of breathlessness and co-morbidity correlated significantly with low motivation. Studies have shown that doing activities that are enjoyable promotes PA in daily life, indicating that activities that enhance motivation might help people with COPD to see PA as part of their life rather than an obligation. Further exploratory studies are needed.

[Antifibrotic therapy in other fibrotic interstitial lung diseases than idiopathic pulmonary fibrosis].

Numerous studies have shown that perioperative heparin bridging in patients treated with a vitamin K antagonist leads to an increased incidence of bleeding and so far, there is no evidence that it leads to a significant reduction in postoperative thromboembolism as summarised in this review. Prophylactic dosage of heparin is recommended after major surgery. Heparin bridging is not relevant in patients receiving a direct oral anticoagulant due to the rapid onset and offset of action of DOACs.

Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial.

BACKGROUND: The trans-membrane protease serine 2 (TMPRSS2) is essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and infection. Efficacy and safety of TMPRSS2 inhibitors in patients with coronavirus disease 2019 (Covid-19) have not been evaluated in randomized trials. METHODS: We conducted an investigator-initiated, double-blind, randomized, placebo-controlled multicenter trial in patients hospitalized with confirmed SARS-CoV-2 infection from April 4, to December 31, 2020. Within 48 h of admission, participants were randomly assigned in a 2:1 ratio to receive the TMPRSS2 inhibitor camostat mesilate 200 mg three times daily for 5 days or placebo. The primary outcome was time to discharge or clinical improvement measured as ≥2 points improvement on a 7-point ordinal scale. Other outcomes included 30-day mortality, safety and change in oropharyngeal viral load. FINDINGS: 137 patients were assigned to receive camostat mesilate and 68 to placebo. Median time to clinical improvement was 5 days (interquartile range [IQR], 3 to 7) in the camostat group and 5 days (IQR, 2 to 10) in the placebo group (P = 0·31). The hazard ratio for 30-day mortality in the camostat compared with the placebo group was 0·82 (95% confidence interval [CI], 0·24 to 2·79; P = 0·75). The frequency of adverse events was similar in the two groups. Median change in viral load from baseline to day 5 in the camostat group was -0·22 log10 copies/mL (p <0·05) and -0·82 log10 in the placebo group (P <0·05). INTERPRETATION: Under this protocol, camostat mesilate treatment was not associated with increased adverse events during hospitalization for Covid-19 and did not affect time to clinical improvement, progression to ICU admission or mortality. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001200-42.

[Malignant pleural mesothelioma].

Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. The disease is of importance, since the incidence in Denmark is increasing despite cessation of the use of asbestos in the 1980s. MPM has a long latency period, and the first symptom is often dyspnoea, typically caused by pleural effusion. The diagnosis is a challenge, because cytology often is non-conclusive, and thoracoscopy is needed to obtain biopsies for immunohistochemistry. The occupational history is important, since the patients are entitled to compensation. The treatment is often limited to palliation.

Autoimmune pulmonary alveolar proteinosis in an adolescent successfully treated with inhaled rhGM-CSF (molgramostim).

Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare parenchymal lung disease characterized by accumulation of surfactant in the airways with high levels of granulocyte-macrophage colony stimulating factor (GM-CSF) antibodies in blood. Disease leads to hypoxemic respiratory failure. Whole lung lavage (WLL) is considered the first line therapy, but procedure can be quite demanding, specifically for children. Recently alternative treatment options with inhaled GM-CSF have been described but no consensus about the standard treatment exists. We here describe a unique case of a 14-year-old patient who was successfully treated with WLL and subsequent inhalations with molgramostim - new recombinant human GM-CSF (rhGM-CSF).

Familial idiopathic pulmonary fibrosis in a young female.

Idiopathic pulmonary fibrosis is a chronic interstitial lung disease of unknown cause. In the past years there have been observations of clustering of pulmonary fibrosis in families, indicating the disease can be inherited. The most commonly identified mutations are mutations involving proteins from the telomerase complex and the surfactant system, where the mutations from the surfactant protein system are less identified. We report a rare care of familial IPF in a young female at the age of 34 years, in whom genetic testing shows two different heterozygous variants for the surfactant protein system as a probable cause of her interstitial lung disease.

Barriers and motivational factors towards physical activity in daily life living with COPD - an interview based pilot study.

Background: In Denmark, few people with Chronic Obstructive Pulmonary Disease (COPD) engage in physical activity although it is evident that pulmonary rehabilitation has positive effects on physical activity, dyspnoea, anxiety, fatigue and quality of life. Objective: The purpose of this pilot study was to explore why people with COPD do not engage in physical activity and to explore motivational factors and barriers towards physical activity. Furthermore, to explore the role general practitioners have in this matter. Design: We conducted fieldwork among five people with COPD and three general practitioners using qualitative semi-structured interviews. We made a thematic analysis and our analytical perspective was based on The Health Belief Model and Self Determination Theory. Results: Findings revealed that people with COPD was not active because they did not receive the necessary information from the general practitioners about the benefits of physical activity neither about the negative consequences of an inactive lifestyle. Motivational factors were knowledge about COPD and benefits of physical activity. Experiencing the benefits on their own bodies, feeling that it was not dangerous to feel breathless and being successful coping with breathlessness were motivational. Functional tests like walking tests were very important and motivational for the participants because they outlined the progress achieved during activity and provided evidence of progress that was easy to comprehend compared with spirometry tests. General practitioners did not inform about the benefits of physical activity because they felt that medication was more important than physical activity and that people with COPD would not be motivated to be active. Conclusions: The main reason for people with COPD not being physically active in our study was lack of sufficient information from their general practitioners. This study described some barriers, enablers and motivational factors for a physically active lifestyle and the general practitioners' role in this. Thus, it is important that people with COPD receive early information about physical activity - and it should start with the general practitioners, who are the gate keepers in the health care system. We recommend that lung function test results are never used as a single indicator of disease progression and that more focus should be paid to functional tests like The Shuttle Walking Test or The Six Minute Walking Test.Further studies to identify barriers to, and facilitators for referral people with COPD to physical activity in daily life from the perspective of Danish general practitioners are required.